Computational Insight into Biotransformation Profiles of Organophosphorus Flame Retardants to Their Diester Metabolites by Cytochrome P450

Biotransformation of organophosphorus flame retardants (OPFRs) mediated by cytochrome P450 enzymes (CYPs) has a potential correlation with their toxicological effects on humans. In this work, we employed five typical OPFRs including tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), tris(1-chloro-2-propyl) phosphate (TCIPP), tri(2-chloroethyl) phosphate (TCEP), triethyl phosphate (TEP), and 2-ethylhexyl diphenyl phosphate (EHDPHP), and performed density functional theory (DFT) calculations to clarify the CYP-catalyzed biotransformation of five OPFRs to their diester metabolites. The DFT results show that the reaction mechanism consists of Cα-hydroxylation and O-dealkylation steps, and the biotransformation activities of five OPFRs may follow the order of TCEP ≈ TEP ≈ EHDPHP > TCIPP > TDCIPP. We further performed molecular dynamics (MD) simulations to unravel the binding interactions of five OPFRs in the CYP3A4 isoform. Binding mode analyses demonstrate that CYP3A4-mediated metabolism of TDCIPP, TCIPP, TCEP, and TEP can produce the diester metabolites, while EHDPHP metabolism may generate para-hydroxyEHDPHP as the primary metabolite. Moreover, the EHDPHP and TDCIPP have higher binding potential to CYP3A4 than TCIPP, TCEP, and TEP. This work reports the biotransformation profiles and binding features of five OPFRs in CYP, which can provide meaningful clues for the further studies of the metabolic fates of OPFRs and toxicological effects associated with the relevant metabolites.     

Promising Chemotherapy for Malignant Pediatric Brain Tumor in Recent Biological Insights

Brain tumors are the most widespread malignancies in children around the world. Chemotherapy plays a critical role in the treatment of these tumors. Although the current chemotherapy process has a remarkable outcome for a certain subtype of brain tumor, improving patient survival is still a major challenge. Further intensive treatment with conventional non-specific chemotherapy could cause additional adverse reactions without significant advancement in survival. Recently, patient derived brain tumor, xenograft, and whole genome analysis using deep sequencing technology has made a significant contribution to our understanding of cancer treatment. This realization has changed the focus to new agents, targeting the molecular pathways that are critical to tumor survival or proliferation. Thus, many novel drugs targeting epigenetic regulators or tyrosine kinase have been developed. These selective drugs may have less toxicity in normal cells and are expected to be more effective than non-specific chemotherapeutics. This review will summarize the latest novel targets and corresponding candidate drugs, which are promising chemotherapy for brain tumors according to the biological insights.     

Rapid Detection of Five Estrogens Added Illegally to Dietary Supplements by Combining TLC with Raman Imaging Microscope

Estrogens added illegally to dietary supplements are hazardous to human health. Traditional detection and analysis methods have many limitations, and we have developed an assay that combines thin-layer chromatography with Raman imaging microscopy (TLC-RIM). The five estrogens (estrone, estradiol, estriol, ethinyl estradiol, and diethylstilbestrol) were initially separated by TLC, then detected by area scanning Raman imaging with a 532 nm laser under a microscope. Raman spectra were obtained for each estrogen, which were used for detecting estrogen illegally added to botanical dietary supplements. The LOD of each estrogen was 0.4, 1.0, 0.8, 0.2, and 0.2 mg/mL, respectively. The matrix in the real sample did not interfere with the detection of estrogens. The method was fast, sensitive, stable, specific, and reliable.     

Effect of biaxial strain and hydrostatic pressure on the magnetic properties of bilayer CrI3

Two-dimensional van der Waals magnetic materials are intriguing for applications in the future spintronics devices, so it is crucial to explore strategy to control the magnetic properties. Here, we carried out first-principles calculations and Monte Carlo simulations to investigate the effect of biaxial strain and hydrostatic pressure on the magnetic properties of the bilayer CrI₃. We found that the magnetic anisotropy, intralayer and interlayer exchange interactions, and Curie temperature can be tuned by biaxial strain and hydrostatic pressure. Large compressive biaxial strain may induce a ferromagneticto-antiferromagnetic transition of both CrI₃ layers. The hydrostatic pressure could enhance the intralayer exchange interaction significantly and hence largely boost the Curie temperature. The effect of the biaxial strain and hydrostatic pressure revealed in the bilayer CrI₃ may be generalized to other two-dimensional magnetic materials.     

Non-Invasive Detection of Anti-Inflammatory Bioactivity and Key Chemical Indicators of the Commercial Lanqin Oral Solution by Near Infrared Spectroscopy

Quality control methods of current traditional Chinese medicine (TCM) preparation is time-consuming and difficult to assess in terms of overall efficiency of the drug. A non-destructive rapid near-infrared spectroscopy detection system for key chemical components and biological activity of Lanqin oral solution (LOS), one of the best-selling TCM formulations, was established for comprehensive quality evaluation. Near infrared spectral scanning was carried out on 101 batches of commercial LOS under the penetrated vial state and traditional state. RAW 264.7 cells were cultured to detect the anti-inflammatory ability of LOS, and the reference concentrations of epigoitrin, geniposide, and baicalin were obtained by HPLC. The quantitative models were optimized by three kinds of variable selection methods. The correlation coefficients of prediction value of the models were greater than 0.94. The system also passed the external validation. The performance of the non-invasive models was similar to the traditional models. The established non-destructive system can be applied to the rapid quality inspection of LOS to avoid unqualified drugs from entering the market and ensure drug effectiveness. The biological activity index of LOS was introduced and predicted by NIRs for the first time, which provides a new idea about the quality control of TCM formulations.     

Production, Characterization, and Application of an Organic Solvent-Tolerant Lipase Present in Active Inclusion Bodies

An organic solvent-tolerant lipase from Serratia marcescens ECU1010 (rSML) was overproduced in Escherichia coli in an insoluble form. High concentrations of both biomass (50 g cell wet weight/L culture broth) and inclusion bodies (10.5 g/L) were obtained by applying a high-cell-density cultivation procedure. Activity assays indicated that the enzymatic activity of rSML reached 600 U/L. After treatment with isopropyl ether for 12 h, the maximum lipase activity reached 6,000 U/L. Scanning electron microscopy and Fourier transform infrared microspectroscopy revealed the activation mechanism of rSML in the presence of organic solvents. rSML was stable in broad ranges of temperatures and pH values, as well as in a series of organic solvents. Besides, rSML showed the best enantioselectivity for the kinetic resolution of (±)-trans-3-(4-methoxyphenyl)glycidic acid methyl ester. These features render the S. marcescens ECU1010 lipase attractive for biotechnological applications in the field of organic synthesis and pharmaceutical industry.     

Molecular dynamics studies of ultrafast laser-induced nonthermal melting

Molecular Dynamics (MD) is employed to investigate nonthermal melting triggered by coherent phonon excitation in bismuth telluride, which has Peierls distortion in the lattice structure. Results showed that the structural distortion caused by coherent phonons appears as early as 80 fs, while it takes several picoseconds for the whole phonon-excited area to evolve into a liquid state. It was also found that the temperature in the phonon-excited area rises quickly within tens of femtoseconds, while the rest of the lattice remains at the initial temperature even after several picoseconds, which is separated from the high temperature region across a thin transition area. This phenomenon is analogous to the heat transfer across a solid–liquid interface, even though in our case there is no abrupt solid-liquid interface between the cold lattice and the quasiliquid.     

Direct Henry reactions with modified calcium oxide as solid catalyst

Commercial CaO was modified simply with benzyl bromide. The modified CaO had good water resistance, and characterization by FTIR and TG revealed the modifier was chemically bonded to the CaO surface. Commercial CaO and CaO modified with benzyl bromide were investigated as catalysts for the Henry reaction between benzaldehyde and nitromethane. It was found that the catalytic activity of the modified CaO was greatly improved, with high conversion of benzaldehyde to the (E)-phenyl nitroolefin and 1-phenyl-2-nitroethanol, and with different selectivity from commercial CaO. The effect of modification and reaction conditions on yield, selectivity, and mechanism were studied thoroughly.